4-amino-1-(2-cyano-2-deoxy-β-D-arabinofuranosyl)-2(1H)-pyrimidinone (CNDAC; See the Formula I below) is an antimetabolite in which the 2′-β position of deoxycytidine ribose is replaced by a cyano group.

CNDAC is a deoxycytidine analog, which at the time of filing of this application, is synthesized in Japan. Unlike deoxycytidine derivatives (gemcitabine) which are widely clinically used, CNDAC primarily causes DNA strand breaks. Specifically, it is considered that CNDAC is phosphorylated by intracellular deoxycytidine kinase, and thereby a triphosphorylated form (CNDACTP) is provided; that CNDACTP is incorporated into a DNA strand, thus inducing hydrolysis and breaking the DNA strand; and that the cell cycle is thus arrested at the G2/M phase and the cell is killed. (See, for example, Japanese Patent Publication No. 2559917; J. Med. Chem., 1991, 34 (9): 2917-9; and J. Med. Chem., 1993, 36 (26): 4183-9.)
Most antitumor agents, which have an inhibitory effect on DNA synthesis as a main effect and are widely clinically used, demonstrate the effect as exhibiting the inhibitory effect at the S phase. Different from relatively fast-growing tumors used in animal tests, however, it has been identified that tumors grow slowly in clinical circumstances and that there are few cells in the S phase. Meanwhile, the antitumor effect of CNDAC, which is achieved by the DNA strand break effect, eventually arrests the cell cycle at the G2/M phase and thus kills tumor cells. Accordingly, it is considered that CNDAC can be differentiated from DNA synthesis inhibitors in wide clinical use, and that CNDAC is a clinically effective antitumor agent (Molecular Pharmacology, 2001, 59 (4): 725-31).
In order to achieve a higher antitumor effect of CNDAC for clinical use, it is necessary to develop a highly effective treatment method that enables continuous medication and surely prolongs patient survival.